GSK1059615 / GSK - LARVOL DELTA

INHIBITION OF PI3K AND MTOR BY GSK1059615 AS A THERAPEUTIC CONTENDER AGAINST A Β AGGREGATION IN EARLY -ONSET ALZHEIMER'S DISEASE (ADPD 2025) - "Pharmacological inhibition of PI3K/mTOR by GSK1059615 improved cognitive performance and neuronal health in AD mice models without adverse effects. GSK1059615 administration yielded key reductions beyond A β plaque deposition, displaying neuroprotective eff ects on early -onset AD. Fu rther investigations are warranted to explore our findings' clinical translatability."

Alzheimer's Disease • CNS Disorders • Inflammation

Screening of potential targets and small-molecule drugs related to lipid metabolism in ovarian cancer based on bioinformatics. (PubMed, Biochem Biophys Res Commun) - "six OC potential genes related to lipid metabolism were identified and verified, which can be used as potential biomarkers and therapeutic targets to evaluate the prognostic risk of OC patients. In addition, three small-molecular drugs that may be effective in the treatment of OC were unearthed, among which Cephaeline has the most potential. We speculate that Cephaeline may target six genes to inhibit progression of OC by affecting lipid metabolism."

Journal • Metabolic Disorders • Oncology • Ovarian Cancer • Solid Tumor • CPT1A

Quantitative Proteomics Characterization of the Effect and Mechanism of Trichostatin A on the Hippocampus of Type II Diabetic Mice. (PubMed, Cell Mol Neurobiol) - "Diabetic encephalopathy (DE) is one of the complications of diabetes mellitus with mild-to-moderate cognitive impairment. In conclusion, our study revealed that CAT and PRKAA2 were the key proteins involved in the improvement of DE after TSA treatment. ISOX, apicidin, and panobinostat were promising similar drugs and that GSK-1059615, alisertib, and avrainvillamide-analog-6 were promising ancillary drugs to TSA in the treatment of DE."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • Vascular Neurology • CANX • NPM1 • PRKAA2 • UBA52

Nanoparticles Loaded with GSK1059615 Combined with Sorafenib Inhibited Programmed Cell Death 1 Ligand 1 Expression by Negatively Regulating the PI3K/Akt/NF-κB Pathway, Thereby Reversing the Drug Resistance of Hepatocellular Carcinoma to Sorafenib. (PubMed, J Biomed Nanotechnol) - "PLGA-PEG-mal diblock copolymer was used to load GSK1059615 and sorafenib, and the vector was further modified with GPC3 antibody (hGC33) to obtain hGC33-modified GSK1059615 and sorafenib-loaded nanoparticles (Ab-G/S-NP). Ab-G/S-NP regulated the activation of cellular signaling pathways in HCC cells by inhibiting the expression and activation of NF-κB and downregulating the level of programmed cell death 1 ligand 1(PD-L1) to reverse drug resistance of HCC cells to sorafenib. These findings deserve further study in the combined treatment of HCC cells with GSK1059615 in vivo to develop a more effective treatment of sorafenib-resistant cancers."

IO biomarker • Journal • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • GPC3 • PD-1 • PD-L1

Cotargeting CHK1 and PI3K Synergistically Suppresses Tumor Growth of Oral Cavity Squamous Cell Carcinoma in Patient-Derived Xenografts. (PubMed, Cancers (Basel)) - "The antitumor efficacy of CHK1 inhibitors (PF477736, AZD7762, LY2606368) and PI3K inhibitors (BYL719, GDC0941, GSK1059615) was investigated in OSCC cell lines and PDX models. Furthermore, compared with monotherapy, cotreatment with CHK1 and PI3K inhibitors exerted synergistic anticancer effects by suppressing CHK1, AKT, and 4E-BP1 phosphorylation. In summary, our study identified CHK1 and PI3K as promising targets, especially in a dual treatment strategy combining a CHK1 inhibitor with cisplatin or a PI3K inhibitor as a novel therapeutic approach for OSCC patients with aberrant cell cycle regulation and PI3K signaling activation."

Clinical • Journal • Oncology • Oral Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • EIF4EBP1 • PIK3CA • PIK3CD

Glucose restriction reverses the Warburg effect and modulates PKM2 and mTOR expression in breast cancer cell lines. (PubMed, Cell Mol Biol (Noisy-le-grand)) - "GSK1059615 does not significantly modulate lactate secretion and glucose uptake in both cell lines. Glucose restriction contribute to the reduction of the Warburg effect through mTOR inhibition and regulation of PKM2 kinases."

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Inhibition of gastric cancer cell growth by a PI3K-mTOR dual inhibitor GSK1059615. (PubMed, Biochem Biophys Res Commun) - "AKT-mTOR inhibition and LMX1A upregulation were detected in AGS xenograft tissues with GSK1059615 administration. Together, we conclude that GSK1059615 inhibits GC cell growth in vitro and in vivo."

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Elucidating the transcriptional program of feline injection-site sarcoma using a cross-species mRNA-sequencing approach. (PubMed, BMC Cancer) - "(1) Window-based analysis of mRNA-seq data can uncover SCNAs. (2) The transcriptome of FISS-derived cells is highly consistent with that of FISS tumors. (3) FISS is highly similar to soft-tissue sarcomas in dogs and humans, at the level of gene expression. This work underscores the potential utility of comparative oncology in improving understanding and treatment of FISS."

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